Atherosclerosis is the most common cause of coronary heart disease, including angina pectoris and heart attacks. Atherosclerosis is also a major cause of strokes. Atherosclerosis is characterized by a buildup of fatty deposits, called plaques, on the inner walls of arteries and a resulting decrease in the normal flow of the blood through the artery. These plaques are made up of cholesterol and other lipids. Low density lipoproteins (LDL) are the major carriers of cholesterol in the blood and are believed to be responsible for mediating the arterial accumulation of cholesterol that causes Atherosclerosis. The subendothelial accumulation of LDL is a major atherosclerosis initiating event.
Low density lipoproteins (LDLs) are roughly spherical complexes of lipids and proteins. The predominant protein constituent of LDL is Apolipoprotein B-100 (ApoB100). L. Chan (1992) J. Biol. Chem. 267, 25621-25624. LDL represents only one of a large class of lipoproteins. Other lipoproteins, in order of increasing 5 density, include: chylomicrons, very low-density lipoprotein (VLDL), low-density lipoprotein (LDL), high- density lipoprotein (HDL), and very high-density lipoprotein (VHDL).
Several lipoproteins have also been implicated in the etiology of atherosclerosis. For example, lipoprotein lipase (LpL) has been shown to have multiple interactions with lipoproteins and components of the blood vessel wall. U. Saxena et al. (1992) J. Clin. Invest. 89, 373-380. In particular, LpL has a lipid-binding domain that binds to VLDLs and LDLs with higher affinity than high- density lipoproteins. S. Choi et al. (1995) J. Biol. Chem. 270, 8081-8086. LpL is also able to associate with proteoglycans in the subendothelial cell matrix of blood vessels. It's been shown that these interactions allow LpL to increase LDL binding to blood vessels and thereby act as an atherogenic factor. J. C. Rutledge, M. M. Woo, A. A. Rezai, L. K. Curtiss, I. J. Goldberg (1997) Circulation Research 80, 819-828.
The polypeptide components of lipoproteins are called apolipoproteins and are synthesized mainly in liver and intestinal mucosal cells. Apolipoproteins exists in several divisions, including the B Apolipoproteins (ApoB). ApoB48, which contains 2,152 amino acids, is required for chylomicron formation in the intestine. L. Chan (1992) J. Biol. Chem. 267, 25621-25624.
ApoB100, which contains 4,536 amino acids, is required for assembly of VLDL in the liver. M. M. Veniant, V. Pierotti, D. Newland, C. M. Cham, D. A. Sanan, R. L. Walzem (1997) J. Clin. Invest. 100, 180-188. Other variants of apoB include apoB23, apoB36, and apoB53. J. Kruezer, A. L. White, T. J. Knott, M- L. Jien, M. Mehrabian, J. Scott, S. G. Young, and M. E. Haberland (1997) J. Lip. Res. 38, 324-342. The amino-terminal sequences of apoB tend to be conserved.